Dr. Justin Marchegiani and Evan Brand in today’s podcast talk about functional medicine lab testing where they differentiate the conventional lab testing from the functional testing. This conversation picks up diagnoses done by endocrinologists and about functional imbalance.

Find out what functional medicine doctors and specialists see when they look at conventional lab tests. Learn what adrenal dysfunction is compared to Addison’s or Cushing’s disease. Discover why the functional medicine testing for thyroid is different from your simple conventional TSH test and why you shouldn’t self-treat with hormones and the need to work with a functional medicine specialist when doing so.

Evan Brand: I–I’m actually running out. I’m getting close to running out. I’ve been sending out some invites to different companies to send me some samples so I can find one to carry, but I don’t have those in the mail yet.

Dr. Justin Marchegiani: Very cool. Well, today we are in overdrive. We just did an awesome podcast on Tom Brady’s diet and lifestyle secrets. So if you haven’t listened to that, check that out. We’re going two in a row today. We got–we’re cooking with fire. So today we’re gonna be talking about some functional medicine lab testing, kinda differentiating the conventional lab testing from the functional testing. I get these questions a lot from my patient. You do as well. So we’re gonna kind of get to the bottom of it here today.

Evan Brand: Yeah, so I had a guy last week and he was so confused and conflicted on how he could go to his endocrinologist and get a perfect bill of health. He gets his cortisol measure done via blood and he is perfect, maybe even high. He may have even appeared high on that blood test so he thinks high cortisol is the problem or maybe that he doesn’t have that much of a problem at all. But then when we run the functional test for salivary adrenal hormones for cortisol, he’s low all day in his output. I believe his cortisol sum was 7 units, which is just a fraction of where it should be and he was like, “Oh, my God. This doesn’t make sense. My blood said I was fine.” And that’s it–that’s a very common thing that you and I both experience is people get these blood tests and they get the perfect bill of health, come back next year for your blood work and you’ll be just fine. And that’s a very poor way to keep track of your health.

Dr. Justin Marchegiani: Absolutely. So this person more than likely went to their endocrinologist, and first things first, right? Endocrinologist are not these gods about hormones, right? They aren’t. Endocrinologist are really good and awesome at treating endo–endocrine diseases, right? We’re talking severe disease, especially tumors, especially hyperthyroid conditions. They’re good at picking it up and detecting it. Now we can argue about, you know, pituitary issues, too, right? We can argue about maybe their treatments aren’t the most effective; a lot of times, it’s gonna evolve especially with the thyroid, cutting of the gland out or destroying it with radioactive iodine, et cetera. And again, a lot of the other conditions, it’s typically let’s say they find a–a tumor on the genitals or in the testicles, they remove the testicle. Great, you’re on hormones now for life. The question is, what if we have a functional imbalance? That’s the issue, right? What if we have a functional imbalance? Or what if–what if we have–we’re not diabetic but we’re kinda in between–we’re pre-diabetes, right? A lot of endocrino– or all the endocrinologists diagnose diabetes, too, right? But they’re just giving them Glucophage, metformin, maybe if they progress long enough, they’re giving them insulin, right? Whether it’s long-acting or short–short-acting insulin to cover up all the sugar in their blood stream. So these docs, they’re just kinda managing diseases. They’re doing a good job when it comes to certain things like pulling out a thyroid during maybe Graves’ disease to kind of avoid a thyroid storm. They’re trying to, you know, prevent that these rare things, but we wanna pop in here and use functional medicine because functional medicine, one, it’s very conservative. It’s more cost-effective and a lot of times when it comes to your thyroid, we’re gonna be able to keep your thyroid gland, especially if we’re able to make diet and supplement changes. When it comes to diabetes, we can almost reverse diabetes by just changing our diet, by giving nutrients to help make our body more sensitive to blood sugar. So when you look at endocrinology from a functional perspective, we’re doing different things. It’s a different perspective, right? So we just gotta know what we’re looking at when you go see a functional medicine doctor that’s utilizing a functional endocrinology. We’re looking at functional imbalances that may lead up to disease or pathology, right? Pathology is the realm of the endocrinologist MD. The functional doctor, they’re gonna be at that–in that functional range. And that’s where most people lie and most people that are–go to the doctor, come back home after being told they’re fine, it’s all in their head, or “Hey, you know, here’s this anti-depressant,” or “Hey, you got this hormone issue, here’s a birth control pill.” Those are the people that are gonna do really well, would be seeing a functional medicine doctor or nutritionist.

Evan Brand: Yeah, perfect, perfect way to–to start that thing because many people will–they’ll send over their blood work to us and we’ll look at it and we’ll see things, I mean, you know, we’ll look at blood chemistry and that’s helpful because you can’t get some good measures, you know, HSCRP or inflammation and vitamin D status is helpful to checking your blood and things like that. But generally speaking, most of these measures are just kind of giving you a false sense of–of–of I guess, not a false sense of hope but maybe a false sense of health. I mean, a lot of these markers, your body is gonna go through incredible things to make sure that say, your sodium and your potassium and your magnesium levels–most of those times, those numbers are not gonna change unless there’s a severe, severe issue and you really don’t have the same sensitivity as basically what you were kind of alluding to, is what we’re looking for–very sensitive, very small fractions of hormones and things like that compared to the bigger picture that that doesn’t really provide as much info.

Dr. Justin Marchegiani: Yeah, and all functional issues or functional symptoms, meaning I’m tired but I could still get up and go to work, that’s different than Addison’s disease where your adrenals are totally exhausted. That’s where the endocrinologist focuses on and again, it’s like black and white. If you’re not on that, you know, one side of the spectrum or the other, you’re told you’re normal even if you’re creeping towards one side or the other. So we wanna really elucidate are you heading in the direction of pathology; you may never even get there, but we know that the symptoms are there and that we could start basically putting the car in reverse and going backwards which is analogous to healing. So with this person’s test that you talked to me about pre-show, I think they got a serum-based cortisol test. Is that correct?

Evan Brand: Exactly.

Dr. Justin Marchegiani: So you’re typical endocrinologist is using serum-based cortisol to look at adrenal function from an Addison’s or Cushing’s perspective, right? Cushing’s think push–cortisol is pushed up high–cush, push. And Addison’s disease is adrenal failure where cortisol is really, really low. So they’re looking for super, super high cortisol, typically drive by a lot of times a pituitary tumor sometimes, right? Or a adrenal tumor. And number two, they’re looking for adrenal failure and then a lot of times, they’ll give you a ACTH stimulation test where they give you some compound that stimulates the adrenals to make a whole bunch of cortisol and if the cortisol from the adrenals doesn’t double or increase significantly, then the adrenal glands–something’s wrong with it, right? And that’s where Addison’s comes in to play. That’s the ultimate adrenal failure. Now if you’re working with us or you’re working with functional medicine doctors, you probably head this word adrenal fatigue before. Now we’re not talking about Addison’s or Cushing’s here. So I just wanna make sure we’re on the same page. We’re talking about a functional imbalance that exist in between these two spectrums which conventional medicine, your conventional endocrinologist ignores, is the adrenal dysfunction. And I’m using the word adrenal dysfunction more than fatigue because well, fatigue kinda gives you that–it feels like failure, right? I’m fatigued, I’m fail–it–it’s, you know, working to fatigue, working to failure if we’re in the gym, right? And it’s not quite the same thing. So dysfunction is great because dysfunction does a couple of things. It looks at the cortisol rhythm for instance. So if we’re just doing that sample cortisol serum test, that’s not really giving us the information we want about the adrenals because we don’t have the rhythm aspect to it. Just going to get your blood drawn by itself is a stressor which could increase cortisol. So maybe that cortisol is a lot better than what it would be because that needle created a stress response, i.e. increased the cortisol and then number three, is we’re not looking at that cortisol throughout the day. We don’t have a morning, noon, afternoon, nighttime level just because of the fact that just getting pricked 4 x a day will be really difficult and–and tough and that would alter the test just by–by itself. So we are missing those couple of pieces and also when we’re looking at saliva-based testing, we’re looking at free fraction, meaning a serum-based test is looking at 100% of the hormone coming out of the gland, where saliva is looking at 2% of what’s biologically free, meaning what’s not bound up by protein, whether it’s albumin or globulin. So 2% of the hormone is free. Saliva looks at that. Blood for the most part unless it says serum-free, it’s gonna be looking at 100% of the hormone. And that’s helpful when you’re looking at glandular dysfunction from a disease or cancer-based perspective, not helpful when you’re looking at functional because it’s the free fraction that can bind the receptor site and hormones work like a lock and key. The lock–or the key has to go into the lock for it to work. Same like the free fraction of the hormone that has to go into the hormone receptor site dock and then create that metabolic, anabolic, or anti-inflammatory effect, whether we’re talking about testosterone, progesterone, estrogen, or cortisol.

Evan Brand: Yeah, and so this guy, he couldn’t put a finger on why he was feeling so exhausted noon and afternoon. So he goes in the morning and gets to this cortisol measured on with his blood and, you know, he’s told that he’s fine. But once we actually run this functional adrenal profile on him and see how tanked that he truly is, his noon level was equivalent to my midnight level and I’ve tested myself, and you know, you and I both are always running tests on ourselves just to make sure we’re–we’re staying in the right place. He had–I think it was .7 units of output for noon which–

Dr. Justin Marchegiani: It’s terrible.

Evan Brand: That’s even worse than–that’s even less than you would normally output at midnight and I told this guy. I said, “Man, I’m honestly not surprised based on this reading here that you are able to continue working and you don’t have to just go home and take a nap with this rate.”

Dr. Justin Marchegiani: Exactly and most people that have energy issues and they’re going to see their–their doctor or their endocrinologist, they’re primarily looking at 2 things. Maybe adrenals, maybe they’ll run that serum-based cortisol and if that cortisol’s low, they’ll–they’ll made you an ACH–ACTH stim test. Or number two, they may just run a simple TSH. That’s a thyroid stimulating hormone test. And they’ll look at how high their pituitary is, talking to their thyroid, right? The higher it is, right? That means, the lower the thyroid’s outputting or their output is. So it’s kind of an opposite thing. High TSH means low thyroid. Now that’s important because once that’s ruled out, let’s say your TSH–let’s say your TSH is 4. In functional medicine world, that’s pretty darned high. Anything above 3, we start getting concerned. Let’s say their cortisol’s fine. Well, you’re totally ruled out now for any fatigue issues. You’re gonna be told just go along your merry way, you’re just getting older, or you know, here’s some stimulant medication or they’re gonna say, it’s all in your head, if you just keep coming back. So in our functional world here, we’re looking at thyroid a full spectrum test that involves free fraction, not just TSH, and we’re also gonna be looking at cortisol from a free fraction as well but we’re gonna be looking at the rhythm component and also we’re gonna be looking at DHEA, because DHEA–DHEA-sulfate which is made from the adrenal glands, that’s another indication of adrenal dysfunction. So if DHEA is starting to drop which in a lot people does. Now DHEA is this precursor hormone to a lot of our anabolic hormones. So it’ll precursor to the–it will be a precursor to estrogen in a lot of females and more testosterone in males. And the older we get, the more we rely on DHEA from our adrenals to kind of give us that anabolic push. Now if that’s typically never looked at in a conventional setting because what are you gonna do with that information. So we look at that as well and that gives us a great information, great informative kind of background on what’s happening with the adrenals above and beyond cortisol serum, and also in conjunction with that free fraction, we’re looking at the rhythm of the cortisol, and then we’re also looking at the thyroid, not just TSH, but the whole entire domino line-up, meaning TSH, the T4 free and total, T3 free and total, T3 uptake, reverse T3, and antibody. So we have the trifecta going and if we keep this fatigue pattern going, we’re also wanna look at the mitochondria, which we’ll probably talk about that in a separate podcast. I think we already have but the mitochondria is a really important piece of the puzzle because B vitamins and certain metabolic kreb cycle nutrients are important for fatigue as well and a lot of my patients may have decent mitochondria, or decent adrenals and decent thyroid, but it’s their mitochondria that really is weak. And when we start supporting that with nutrition and we fix the gut issues, it’s amazing how fatigue gets better and better.

Evan Brand: Yeah, so to add to this whole loop–we’ll use the same guy to the example, you know, his DHEA level was actually pretty good. He was at like at a 7.5 which is–

Dr. Justin Marchegiani: It’s good.

Evan Brand: Yeah.

Dr. Justin Marchegiani: It’s really good.

Evan Brand: And–and well, that’s what I thought at first. And he goes, “Oh, and I forgot to put on my–my supplement on my new client paperwork that I’ve been taking 50 mg of DHEA because I read an article a couple of years ago about how good it was for you. So I’ve been basically self-treating with DHEA.” I was like–

Dr. Justin Marchegiani: Oh, forget it. So he’s automatically adrenally fatigued. If he’s at 50 mg and he’s coming up normal or in the–you know, in a good range, that means without it, he’s–doesn’t have a leg to stand on.

Evan Brand: Uh-hmm. Because that’s what–that’s what I was kind of–and I–I wanna break this down a little bit further with you. That’s what I was mind blown about because, you know, I see such a low cortisol sum, I mean, like I said his noon level, he was–he was tanked out on this–on this graph, and I–I could not–I couldn’t really picture what was keeping him afloat. And then we see, okay, so DHEA looks okay and then he tells me that, and I mean, if you were to just go cold turkey on that, he’d probably be in bed rest. What do you think?

Dr. Justin Marchegiani: Absolutely. And also I think his DHEA was probably artificially lowering his cortisol. DHEA biochemically, given without cortisol support can actually lower cortisol. So the fact that he was doing 50 mg which is pretty darn high for a guy by the way, I mean, I like giving much smaller doses, but especially the lower your cortisol is, you actually have to be careful with DHEA because DHEA and cortisol have this seesaw relationship. So if cortisol is lower and DHEA is low, you actually wanna give a lower amount of DHEA just because of the fact you’ll push cortisol even lower which is what I hypothesize happened in this patient’s case.

Evan Brand: Yeah, so it–it’s just amazing and it makes me really wonder and I don’t know what your estimate is, how many people are out there doing this self-treating model, they’re not working with somebody that is actually using functional lab testing and it’s kinda scary because there’s so many people out there and we’ve discussed this before about theory. People talking about theory. Oh, and then in isolation, this thing, DHEA, it–it protects you, it’s good for you, blah blah blah. And everybody goes willy-nilly taking it and that’s not the way to do it and now he’s–he’s on for a long journey. And by the way, he’s 28 years old.

Dr. Justin Marchegiani: Wow.

Evan Brand: With this type. I mean, this is worse than I’ve seen some guy that is 65 years old. I mean, he’s got a worse rhythm, worse output than somebody 40 years older. It’s mind blowing.

Dr. Justin Marchegiani: And DHEA and any hormone in general needs to be given ideally at the lowest physiological level possible. When you go too high, the problem with hormones is, too high of a hormone level can actually create the same symptoms of low hormones, which is kinda where–it’s like wrap your head around that but we have something known as receptor site downregulation where the receptor sites, where hormones dock, actually become numb to the hormone itself. So even if a lot of hormones there, it can actually feel like there’s very little there because the receptor sites become numb to the hormone, because hormones are present in the body at very, very small levels. I mean, these things are measured in like pictograms and nanograms which is like to the billionth and millionth level. So, I mean, very, very sensitive thing, so we wanna treat hormones with the utmost respect. It’s not like taking vitamin C. Oh, I take 1 gram or 3 grams or 5 grams. Who cares, right? Hormones, it’s different. We gotta be very, very careful and use them at the very smallest level as possible ideally and try to use them sublingual as a better way to go just to maximize absorption. If we just give things orally, we tend to have to give 3 to 4 times a higher dose of that hormone because a lot of it gets deactivated by the liver. So when you’re trying to give hormones via a pill that you swallow, you gotta go 3 to 4 times higher because the liver is kind of deactivating things as you put the hormone in your body.

Evan Brand: Makes sense. I mean, could you even call this, sort of like how insulin resistance is when you’re constantly creating these blood sugar spikes and crashes? I mean, would you almost call that hormone resistance or almost like if you were adding in too much GABA for example and you cause a–a downregulation of those production there? What–is that similar to–to what’s going on with DHEA?

Dr. Justin Marchegiani: Yeah, it’s very, very similar. And many patients have this. They are hormones supplementally because they just treat hormones like it’s a nutrient and it’s okay if I give a little bit more of something, but we gotta be careful with hormones and you know, not to mention–not to mention you can give a hormone ‘til the cow comes home but if the diet piece isn’t address, the lifestyle piece isn’t addressed, or there’s an underlying gut or malabsorption thing, then you’re just gonna be, you know, re–you know, addressing icing on the cake, right? You gotta be just re-icing the cake of a cake that’s all moldy underneath, right? We actually–

Evan Brand: Yeah.

Dr. Justin Marchegiani: Wanna fix the underlying issue which should be, you know, the actual foundation of that cake or in our body, our gut and infections and immune and nutrient absorption, not just giving some hormones. And a lot of the anti-aging doctors I find are the most guilty of this.

Evan Brand: Of what?

Dr. Justin Marchegiani: Of just using hormones like supplements and just getting a palliative effect, meaning great, you feel better, awesome, and now you’re done.

Evan Brand: Yeah.

Dr. Justin Marchegiani: And we’re not–we’re not gonna go any deeper.

Evan Brand: Right. Yeah and I mean, that–that’s something that you and I will do is to help with symptoms. Say if they are fatigued, we’ll help get their energy better, but eventually we’ve gotta work backwards far enough or deep enough rather to get to what’s causing it, you know. I mean, it’s tough to tell somebody, “Hey, we have to eliminate your–your gut infection.” Maybe we can’t go straight there but we’ll help you feel better first, so that you actually have the–the motivation to get going to that and I totally agree with you that most people they get cut short and they have all these puzzle pieces, I–I like to use the puzzle now as you were there, it’s like their shuffling all these puzzle pieces on top of the table, but they’re still missing some from the drawer, that 4 drawers down; they never pull that piece out and that’s why they’re–they’re puzzle is never complete and they’re always gonna have some type of lingering symptom or issue.

Dr. Justin Marchegiani: Absolutely, so looking at this person’s test here. Just remember blood test typically if it’s a hormone, it’s always gonna be serum-based and that’s gonna look at 100% of the hormone; it’s ignoring the 2%. So if you want, get the free portion of it, and we can do it via saliva. Some tests we can do it via blood as well. We can order an estradiol free. I don’t think you can do a progesterone free via blood so you have to do that via saliva. We can order a thyroid free, right? T4, thyroxin free. We can order T3 free. So we can do that via saliva. We can do testosterone total and free which is nice. So we have, you know, a lot of latitude with some of the blood testing, and also when we look at blood test, we’re looking at it differently. I mean, the high and low ranges basically are 2.5% of the population, high and low, which we know 95% isn’t normal. So we’re looking at these lab tests functionally speaking which is really important because we want people to be in that middle 30% or so and if you start creeping outside of that, it can mean something where conventional doctor they just look at it and make sure nothing’s flagged which would potentially indicate pathology or something more severe, it depends. When we’re looking at cholesterol, it’s not the case. That’s another podcast. We’ll have–

Evan Brand: Oh yeah.

Dr. Justin Marchegiani: To do that later. Cholesterol is actually one of these markers that’s more overly sensitive and because we’re not looking at other things like inflammation and particle size and–and those things. But for the most part, blood tests are gonna miss a lot of things if you’re not looking at it with a functional medicine eye to it.

Evan Brand: Totally, that’s a great point.

Dr. Justin Marchegiani: Anything you wanna add, Evan?

Evan Brand: No, I mean, this was–this was good. I don’t know if I have much more to say about this topic. I think we’ve crushed it.

Dr. Justin Marchegiani: Alright, well, great podcast. Take home is just understand kinda what your blood test you’re looking at. If you’re getting hormones done, look at free and look at total fraction or serum, you know, fraction as well. And then make sure you have a complete picture, right? Know what the MD is looking at which is disease and pathology and then know what the functional medicine doctor is looking at. They’re looking at functional imbalance. If you get that, then you have the right take home message.

Evan Brand: Yeah, and I–I guess I would add one last thing here, you know, my goal and–and your goal is not to–to instill fear and say that if you have say some blood work that looks like it’s perfect, not to be paranoid and think that I’m not perfect now because of this podcast, but that you do want to reach out to one of us or reach out to someone that knows how to look at this stuff from the functional perspective, that way you’re getting a little bit more help, because my grandfather, for example, I mean, he’s gone year after year after year, and he gets a perfect bill of health on his blood work but once I go over there and put the magnifying glass to it, it’s like, “Wow, look at this! According to here and here and here, you’re super dehydrated. There’s inflammation here and it’s like, ‘No, you’re not perfect bill. We need to dial some things in together.’” And that’s a totally realistic goal and it’s a fun process to do and there’s so much more potential that you can have. So don’t ever sell yourself short and just say that it’s good enough. Be happy. Be happy with where you are but there’s always one little higher bar of where you can likely feel and be with your energy, your sleep, the way you look, your sex drive, I mean everything. There’s–there’s so much more potential out there for you.

Dr. Justin Marchegiani: Well, most patients that I see, they already have symptoms. They’ve gotten this testing done. They go to their MD because well, they’re in their network, why not?

Evan Brand: Yeah.

Dr. Justin Marchegiani: And then they’re looking for answers and then their MD says, “You’re fine.” And then they’re like, “But I know I’m not. Like I felt this slow degradation over the last couple of years, something’s not right.” And then they push it. They come back again. They go to someone in their network. The other doctor sees the notes and they’re like, “Yeah, you’re fine. I think this is all in your head.” And then once that hits or once they’re thrown an anti-depressant or some kind of medication that’s just palliative and just covering up symptom and they know about it. Then they’re BS and then they’re like, “Man, I’m–I gotta go see someone else.” And then once we do the functional testing, it’s a relief once they find a bug or they see some nutrients off, or we find their–their diet’s off or we find something is wrong and then we fix it and they start feeling better. It’s like, “Wow!” So that’s total freedom when we get to the root and then they see improvement versus hey, when you tell someone they’re making something up and they have no reason to make it up because people that are spending money on food and–and really being conscious of things, they’re not making things up. That’s not how it works, right? There’s always something deeper there and people intuitively know it and they don’t need a lab test a lot of times to even say something’s wrong.

Evan Brand: Exactly. I totally agree and I think that’s what helps you and I sleep good at night is because once you help somebody to find that answer or to find that piece of the puzzle that was never looked at deep enough, it’s like, “Oh, my God, I’m finally heard. I’m finally getting an explanation that makes sense of why this is happening. I knew something was–was wrong but I couldn’t identify what it was.” And then just we use a different set of tools and now there’s an answer, and oh gosh, does that feel good!